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PARP1 promotes nucleotide excision repair through DDB2 stabilization and recruitment of ALC1

2012; Rockefeller University Press; Volume: 199; Issue: 2 Linguagem: Inglês

10.1083/jcb.201112132

1540-8140

Alex Pines, Mischa G. Vrouwe, Jurgen A. Marteijn, Dimitris Typas, Martijn S. Luijsterburg, Medine Cansoy, Paul J. Hensbergen, André M. Deelder, Anton de Groot, S. Matsumoto, Kaoru Sugasawa, Nicolas H. Thomä, Wim Vermeulen, Harry Vrieling, Leon H.F. Mullenders,

Genomics and Chromatin Dynamics

The WD40-repeat protein DDB2 is essential for efficient recognition and subsequent removal of ultraviolet (UV)-induced DNA lesions by nucleotide excision repair (NER). However, how DDB2 promotes NER in chromatin is poorly understood. Here, we identify poly(ADP-ribose) polymerase 1 (PARP1) as a novel DDB2-associated factor. We demonstrate that DDB2 facilitated poly(ADP-ribosyl)ation of UV-damaged chromatin through the activity of PARP1, resulting in the recruitment of the chromatin-remodeling enzyme ALC1. Depletion of ALC1 rendered cells sensitive to UV and impaired repair of UV-induced DNA lesions. Additionally, DDB2 itself was targeted by poly(ADP-ribosyl)ation, resulting in increased protein stability and a prolonged chromatin retention time. Our in vitro and in vivo data support a model in which poly(ADP-ribosyl)ation of DDB2 suppresses DDB2 ubiquitylation and outline a molecular mechanism for PARP1-mediated regulation of NER through DDB2 stabilization and recruitment of the chromatin remodeler ALC1.